Randomized Controlled Trial
Study population and setting
This study evaluated the NIH-Moderna SARS-CoV-2 mRNA vaccine in a blinded, placebo-controlled phase 3 clinical trial. At 99 centers across the United States, 28,207 participants (aged 18 years and older) without evidence for current or previous SARS-CoV-2 infection were included in the per-protocol analysis in an approximately 1:1 ratio of vaccine to placebo recipients. The participants were stratified according to age (> 65 or < 65 years), as well as for risk of developing severe COVID-19 disease for those < 65 years only (determined by presence of preexisting conditions per CDC criteria). All analyzed participants received two injections of either 100 μg mRNA-1273 or placebo 28 days apart. The primary endpoint measured was the prevention of first-occurrence, symptomatic, PCR verified SARS-CoV-2 infection at least 14 days following the second injection.
Summary of Main Findings
196 subjects developed laboratory verified COVID-19, with 11 cases in the vaccine group (3.3 per 1,000 person-years) and 185 in the placebo group (56.5 per 1,000 person years), suggesting that a two-dose regimen of the NIH-Moderna SARS-CoV-2 mRNA vaccine is approximately 94.1% effective at preventing COVID-19. As compared to people in the placebo group, people receiving the vaccine were more likely to report local symptoms (pain, redness, and swelling) and systemic events (headache, fever, muscle pain, joint pain, nausea, vomiting, and chills). Local and systemic events were more common after the second dose; symptoms lasted a mean of approximately 2.6–3.2 days. The frequency of symptoms after 28 days were generally similar between the groups. Some level of protection may be afforded following a single dose starting approximately 14-days after the first injection, although the study was not explicitly designed to evaluate this outcome. Consistent with previous trial phases, the vaccine was well-tolerated and side effects were minimal. Additionally, no evidence was found for enhancement of disease following infection in the vaccinated group (e.g., antibody-dependent enhancement or vaccine associated enhanced respiratory disease); on the contrary, the data suggest the vaccine may lessen the severity of COVID-19, as all of the severe cases were in the placebo group. As compared to people in the placebo group, people receiving the vaccine were more likely to report local symptoms (pain, redness, and swelling) and systemic events (headache, fever, muscle pain, joint pain, nausea, vomiting, and chills). Local and systemic events were more common after the second dose; symptoms lasted a mean of approximately 2.6–3.2 days. The frequency of symptoms after 28 days were generally similar between the groups.
The study group was sufficiently large and diverse in terms of age, race, and ethnicity. Numerous secondary end points (e.g., efficacy following a single dose, ability to prevent severe COVID-19, safety, etc.) were included.
As this trial is still ongoing, not all data is available at this time. Data regarding prevention of asymptomatic infections are not reported here. However, these data were collected as per the clinical trial protocol and should be reported in the future. Additionally, increased transparency and data sharing (the current data sharing statement simply says that data ‘may’ be shared at the conclusion of the trial in 2022) are warranted for a study of this magnitude and gravity and would increase the confidence of both the scientific community and the public in the reported results.
The phase 3 trial data published here for one of the two currently authorized and available vaccines in the United States provides crucial and largely reassuring information for vaccine recipients.
This review was posted on: 11 January 2021